非酒精性脂肪性肝病新指南不建议开展筛查

美国胃肠病学会(AGA)、美国肝病研究学会(AASLD)和美国胃肠病学院(ACG)日前联合发布了新版非酒精性脂肪性肝病诊断与治疗指南，向广大医生提出了45项建议。这部新指南同时发表在6月刊《胃肠病学》杂志和《美国胃肠病学与肝病学杂志》上。

指南撰写组主席、印第安纳大学胃肠与肝病科主任Naga Chalasani博士指出，随着肥胖流行情况日益严峻，非酒精性脂肪性肝病(NAFLD)也越来越受到关注。提出这些建议是为了能灵活地用于个体化的患者。该指南还包括对于一般人群和高危人群中NAFLD发病率的讨论，以及对该病自然史的描述（Gastroenterol. 2012年5月15日[doi: 10.1053/j.gastro.2012.04.001]）。

成人筛查与诊断

•根据定义，NAFLD意味着患者目前或最近并未大量摄入酒精。但迄今为止，对“大量”的确切定义仍不明朗。新指南指出，在评估可疑NAFLD患者时，“大量摄入酒精”应该是指男性每周饮酒21份以上，女性每周饮酒14份以上。

• 目前不建议开展NAFLD筛查，不论是在初级保健机构就诊的成人，还是在糖尿病或肥胖专科就诊的高危患者。关于NAFLD的诊断性检查和治疗选择还存在很多不确定性，筛查的远期收益和成本效益也是未知数。

•出于同样理由，目前不建议对NAFLD患者的家属进行筛查，尽管有一些证据提示这种疾病具有一定遗传性而且可能在某些家庭集中发生。

•在对可疑NAFLD患者进行评估时，必须排除其他可能导致脂肪变性的原因，并找出可能存在的肝脏合并症。鉴别诊断时必须考虑到肝炎、药物毒性、Wilson氏病、营养不良、血色病和自身免疫性肝病。

•对于下列患者应考虑行肝脏活检：脂肪性肝炎和进展期肝纤维化风险较高的患者；血清铁蛋白水平持续增高、铁饱和度增加的患者，特别是如果他们携带C282Y基因遗传突变；如果不活检就无法确定其他病因或肝脏合并症的患者。对于其他患者不建议行肝脏活检。

成人患者治疗

•总体重下降至少3%~5%似乎是缓解脂肪变性的必要条件，减少脂肪和体重减轻，要改善坏死性炎症则需要将总体重降低10%。

•不建议使用二甲双胍，原因是该药对于肝脏组织学没有明显影响。

• 已进展为非酒精性脂肪性肝炎(NASH)的NAFLD患者可以使用吡格列酮，但该药的长期安全性和疗效尚不明确，而且合并糖尿病的患者服用吡格列酮的效果从未被研究过。

•维生素E应被视为进展为NASH的NAFLD患者的一线治疗，但不包括合并糖尿病、NASH肝硬化或隐源性肝硬化的患者。

•对NAFLD或NASH均不建议采用熊去氧胆酸治疗，也不建议使用ω-3脂肪酸，但后者可作为NAFLD患者高甘油三酯血症的一线治疗药物。

•NAFLD不是减肥手术的禁忌证，除非患者已被确诊为肝硬化。不过，对于NAFLD患者，“前肠道减肥手术的术式、安全性和疗效”均未确定。

•NASH肝硬化患者应筛查食管静脉曲张，应考虑筛查肝细胞癌。

儿科建议

新的指南专设了一个章节探讨了儿童和青少年中的NAFLD，原因是已有报告称年仅2岁的幼儿即可罹患该病，8岁即可发生NASH相关性肝硬化。

•对于超重和肥胖儿童的NAFLD筛查还不能提出正式建议，原因是支持证据过少。尽管最近有一个专家委员会建议对这一人群每2年进行1次肝病筛查(采用肝酶指标)。

•如果在非常年幼或体重正常的儿童中发现脂肪肝，应评估单一原因的慢性肝病（如脂肪酸氧化缺陷、溶酶体贮积病，以及过氧化物酶病）和成人中的常见病因。

•血清自身抗体滴度高，尤其是当伴随转氨酶、球蛋白水平升高时，需要行肝脏活检以确定是否存在自身免疫性肝炎。

•儿童NAFLD的组织病理学可以不同于成人，可能包含明显的大泡性肝细胞脂肪变性、肝门炎症和肝门纤维化，而无气球样变。

•解决肥胖是治疗的第一步，建议采取强化生活方式干预，不过本次并未推荐具体的饮食或运动计划。

•由于尚未发现二甲双胍对儿童有益，因此不建议对儿童使用该药。

•除非研究能够证实维生素E可改善NASH的肝脏组织学，否则不推荐对儿童使用维生素E。

Chalasani博士及其同事披露与多家公司存在联系，包括研究支持和与NAFLD有关的有偿咨询。

 

A new practice guideline for diagnosing and managing nonalcoholic fatty liver disease has been released jointly in the June issues of Gastroenterology, the American Journal of Gastroenterology, and Hepatology.

The guideline represents a collaboration among three societies – the American Gastroenterological Association, the American Association for the Study of Liver Diseases, and the American College of Gastroenterology – and it includes 45 recommendations for physicians and other clinicians. These recommendations “suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care.” Summaries of the current world literature upon which these recommendations are based are also included.

The recommendations “are intended to be flexible and adjustable for individual patients,” said Dr. Naga Chalasani, chair of the writing group and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis, and his associates.

Nonalcoholic fatty liver disease is becoming an increasing concern as the obesity epidemic continues. The guideline also includes a discussion of the incidence of NAFLD in the general population and in high-risk groups, as well as a description of the natural history of the disorder, Dr. Chalasani and his colleagues said (Gastroenterol. 2012 May 15 [doi: 10.1053/j.gastro.2012.04.001]).

Screening and Diagnosis in Adults

Among the recommendations concerning diagnosis in the guideline are the following points:

• By definition, NAFLD indicates that patients do not have any ongoing or recent intake of significant quantities of alcohol. But until now, the precise definition of “significant” in this context has been uncertain. The guideline states that when assessing patients suspected of having NAFLD, “significant alcohol consumption” should be defined as more than 21 drinks per week in men and more than 14 drinks per week in women.

• Screening for NAFLD is not recommended at this time, either for adults presenting to primary care practices or for high-risk patients attending diabetes or obesity clinics. There are too many uncertainties concerning diagnostic tests and treatment options, and the long-term benefits and cost-effectiveness of screening are not yet known.

• Screening of family members of patients who have NAFLD is not yet recommended for the same reasons, even though there is some evidence suggesting that the disorder is somewhat heritable and can cluster in certain families.

• When evaluating a patient suspected of having NAFLD, it is essential to exclude other possible causes of steatosis as well as to identify possible comorbid liver disease. Hepatitis, medication toxicity, Wilson’s disease, malnutrition, hemochromatosis, and autoimmune liver disease must be considered in the differential.

• Liver biopsy should be considered in patients at risk for steatohepatitis and advanced fibrosis; in those with persistently high serum ferritin and increased iron saturation, especially if they carry genetic mutations in the C282Y gene; and in patients for whom other etiologies or comorbid liver disease cannot be ascertained without a biopsy. Liver biopsy is not recommended in other patients.

Treatment for Adults

Among the guideline’s recommendations concerning treatment are the following:

• It appears that weight loss of at least 3%-5% of total body weight is necessary to reduce steatosis, and that weight loss of 10% is necessary to improve necroinflammation.

• Metformin is not recommended because it has no significant effect on liver histology.

• Pioglitazone can be used in NAFLD patients who have progressed to nonalcoholic steatohepatitis (NASH), but the long-term safety and efficacy of the drug have not been established, and pioglitazone’s effects in patients with diabetes have never been examined.

• Vitamin E should be considered a first-line therapy for NAFLD patients with NASH, but not those who have concomitant diabetes, NASH cirrhosis, or cryptogenic cirrhosis.

• Ursodeoxycholic acid is not recommended for either NAFLD or NASH. Omega-3 fatty acids are not recommended for NAFLD or NASH but may be first-line agents to treat hypertriglyceridemia in patients who have NAFLD.

• Bariatric surgery is not contraindicated unless patients have established cirrhosis, but “the type, safety, and efficacy of foregut bariatric surgery” in NAFLD have not yet been determined.

• Patients with NASH cirrhosis should be screened for gastroesophageal varices and considered for hepatocellular carcinoma screening.

Pediatric Recommendations

The new guideline contains a section devoted to NAFLD in children and adolescents, since the disorder has been reported in children as young as age 2, and NASH-related cirrhosis has been reported in children as young as age 8.

Among the guideline’s recommendations in the pediatric population are the following:

• No formal recommendation regarding screening of overweight and obese children for NAFLD can yet be made because there is too little evidence to support it, “despite a recent expert committee recommendation for biannual screening for liver disease with liver enzyme measurements in this population.”

• Very young or normal-weight children found to have fatty liver should be assessed for monogenic causes of chronic liver disease (such as fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders), as well as the potential causes usually considered among adults.

• High serum titers of autoantibodies, particularly when associated with high aminotransferase and high globulin levels, require a liver biopsy to identify possible autoimmune hepatitis.

• The histopathology of NAFLD in children can differ from that in adults, and can include marked macrovesicular hepatocellular steatosis, portal inflammation, and portal fibrosis in the absence of ballooning.

• Addressing obesity is the first step in treatment, and intensive lifestyle modification is recommended, although no particular diet or exercise program is advocated at this time.

• Metformin is not recommended because it has not been shown to benefit children.

• Vitamin E cannot be recommended for children until confirmatory studies verify that it improves liver histology in NASH.

Dr. Chalasani and his coauthors disclosed relationships with multiple companies; these relationships include research support and paid consulting related to NAFLD.